DEAR EDITOR,
In 1987, Ferrara et al. (Citation1) described the presence of a potent endothelial cell mitogen in the conditioned medium of follicular cells from bovine pituitary. They baptized it as vascular endothelial growth factor (VEGF) and ever since its role has been underscored in vasculogenesis processes – mice with a mutation in VEGF die during gestation – and physiological and pathological angiogenesis – wound healing and tumor vascularization. These functions honor its actual name; nonetheless, its recent functions might demand a novel – and more precise – denomination for this important protein.
The role of VEGF in maintaining adult vasculature has raised attention because of the consequences of its neutralization observed when patients receive anti-VEGF therapy for cancer and in the presence of an inhibitor as seen in preeclamptic patients, who present a high concentration of a soluble form of VEGF receptor 1 – sFlt-1 – which binds free VEGF and blocks its actions. Complications in these patients mainly include hypertension, proteinuria, renal thrombotic microangiopathy, and neurological alterations (Citation2).
In adults, VEGF is expressed in virtually all vascularized tissues. Regularly, VEGF is produced in epithelial cells that abut fenestrated and sinusoidal blood vessels, such as choroid plexus, glomerulus of the kidney, and hepatic sinusoidal. This expression correlates with the presence of VEGF receptor 2 in the adjacent endothelial cells within these organs, thus pointing out the VEGF as an important factor in maintaining the function of these structures (Citation3). To prove this hypothesis, Eremina et al. (Citation2) used conditional gene targeting to delete VEGF from renal podocytes in adult mice resulting in a glomerular injury. Furthermore, neutralization of VEGF in mice generates decreased perfusion of choroid plexus vasculature relating with the appearance of lesions compatible with reversible posterior leukoencephalopathy syndrome: this lesion is also observed in preeclamptic women and in patients under anti-VEGF therapy (Citation3).
VEGF has also been demonstrated to be important for other cells different from the endothelium. Our group (Citation4) previously demonstrated that VEGF is extremely important to promote podocytes – glomerular epithelial cells – survival and to maintain podocytes filtration function in preventing proteinuria in women with preeclampsia.
So, why would it be important to modify the name of this factor? Nobel Prize winner José Saramago stated “(. . .) The Name is an artificial representation of the thing; however it determines its creation. There’s no existence of the thing if there’s no language representation for it” (Citation5). Naming is a complex cognitive process that represents our current limitations and our possibilities in understanding a phenomenon: that is why the name should represent the thing in an accurate and precise manner.
In this regard, the name vascular endothelial growth factor was very precise 20 years ago. It contained the target cells (vascular endothelial) and indicates the function (inducing proliferation) of the factor. Nevertheless, to our current knowledge, it affects diverse cell types, including epithelial cells, and it has a myriad of functions (Citation4) such as permeability of the endothelium and apoptosis inhibitor in epithelial cells.
The current pathophysiology implications of VEGF in preeclampsia context demand a debate about the limitations of its traditional denomination, mostly to overcome our limitations and enhance our future understanding about the role of this promising factor in these women.
Daniel E. Henao
Grupo Reproducción, Universidad de Antioquia,
Calle 62 # 52 – 59, Medellín, Colombia
E-mail: [email protected]
REFERENCES
- Ferrara N, Schweigerer L, Neufeld G, Mitchell R, Gospodarowicz D. Pituitary follicular cells produce basic fibroblast growth factor. Proc Natl Acad Sci USA 1987; 84(16):5773–5777.
- Eremina V, Jefferson JA, Kowalewska J, . VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008; 358(11):1129–1136.
- Maharaj AS, Walshe TE, Saint-Geniez M, . VEGF and TGF-beta are required for the maintenance of the choroid plexus and ependyma. J Exp Med 2008; 205(2):491–501.
- Henao DE, Arias LF, Mathieson PW, . Preeclamptic sera directly induce slit-diaphragm protein redistribution and alter podocyte barrier-forming capacity. Nephron Exp Nephrol 2008; 110(3):e73–e81.
- Saramago J. El nombre y la cosa. Ciudad de México: Fondo de Cultura Económica, 2007.